Lirentelimab Explained
| Drug Name: | Lirentelimab |
| Type: | mab |
| Mab Type: | mab |
| Source: | u |
| Target: | SIGLEC8 |
| Tradename: | AK002 |
| Routes Of Administration: | Intravenous |
| Cas Number Ref: | [1] |
| Cas Number: | 2283348-97-8 |
| Unii: | SWS48LJU3T |
| Kegg: | D11906 |
| Chembl: | 4297878 |
| C: | 6408 |
| H: | 9884 |
| N: | 1700 |
| O: | 2006 |
| S: | 46 |
Lirentelimab (sold under the brand name AK002) is a humanized nonfucosylated monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis. Adverse reactions include infusion reactions, which are mild to moderate and typically occur following the first infusion.
Mechanism of action
In individuals with asthma, Siglec-8 expression is increased on the surface of eosinophils and mast cells in sputum.[2] Lirentelimab depletes eosinophils via antibody-dependent natural killer cell mediated cytotoxicity.
Indications
As of 2023, lirentelimab has no approved indications.[3]
Pharmacology
Lirentelimab is a humanized, nonfucosylated IgG1 monoclonal antibody that targets Siglec-8. Siglec-8 is an inhibitory receptor present on eosinophils and mast cells, with low level expression on basophils.[4] [5] Interleukin-5, granulocyte-macrophage colony stimulating factor, and interleukin-33 enhance anti-Siglec-8 mediated destruction of eosinophils. Lirentelimab inhibits mast cells' IgE-mediated degranulation and de novo synthesis of prostaglandin D2 in vitro.
Adverse events
Mild-to-moderate infusion reactions may occur with lirentelimab, which tend to occur following the first infusion only.[6]
Research
Lirentelimab has been studied for the treatment of chronic spontaneous urticaria, indolent systemic mastocytosis, and severe allergic conjunctivitis.[7]
External links
- Web site: Lirentelimab. U.S. National Library of Medicine . Drug Information Portal .
Notes and References
- Web site: Lirentelimab . KEGG Drug Database .
- Kerr SC, Gonzalez JR, Schanin J, Peters MC, Lambrecht BN, Brock EC, Charbit A, Ansel KM, Youngblood BA, Fahy JV . An anti-siglec-8 antibody depletes sputum eosinophils from asthmatic subjects and inhibits lung mast cells . Clinical and Experimental Allergy . 50 . 8 . 904–914 . August 2020 . 32542913 . 10.1111/cea.13681 . 7610812 . 219702648 . 1854/LU-8706271 . free .
- Dellon ES, Spergel JM . Biologics in eosinophilic gastrointestinal diseases . Annals of Allergy, Asthma & Immunology . 130 . 1 . 21–27 . January 2023 . 35738437 . 10191215 . 10.1016/j.anai.2022.06.015 .
- Dellon ES, Peterson KA, Murray JA, Falk GW, Gonsalves N, Chehade M, Genta RM, Leung J, Khoury P, Klion AD, Hazan S, Vaezi M, Bledsoe AC, Durrani SR, Wang C, Shaw C, Chang AT, Singh B, Kamboj AP, Rasmussen HS, Rothenberg ME, Hirano I . Anti-Siglec-8 Antibody for Eosinophilic Gastritis and Duodenitis . The New England Journal of Medicine . 383 . 17 . 1624–1634 . October 2020 . 33085861 . 7600443 . 10.1056/NEJMoa2012047 .
- Youngblood BA, Brock EC, Leung J, Falahati R, Bryce PJ, Bright J, Williams J, Shultz LD, Greiner DL, Brehm MA, Bebbington C, Tomasevic N . AK002, a Humanized Sialic Acid-Binding Immunoglobulin-Like Lectin-8 Antibody that Induces Antibody-Dependent Cell-Mediated Cytotoxicity against Human Eosinophils and Inhibits Mast Cell-Mediated Anaphylaxis in Mice . International Archives of Allergy and Immunology . 180 . 2 . 91–102 . 2019 . 31401630 . 10.1159/000501637 . 6878738 . free .
- News: Young A . Therapeutic antibody effective in eosinophilic gastritis . 14 December 2020 . Healio . October 29, 2019.
- Johal KJ, Saini SS . Current and emerging treatments for chronic spontaneous urticaria . Annals of Allergy, Asthma & Immunology . 125 . 4 . 380–387 . October 2020 . 31494233 . 7056515 . 10.1016/j.anai.2019.08.465 .
